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Modern therapy of osteoarthritis (OA) consists of four sequential stages and includes non-pharmacological, pharmacological and surgical methods of treatment, and also assumes the possibility of collaborative management of the patient by doctors of different specialties, which allows to optimize the processes of diagnosis and treatment. The article presents simple and convenient algorithms, including diagnostic criteria, options for providing medical care, as well as situations (so-called red flags) that require referral of a patient to a specialist, primarily a rheumatologist. It has been demonstrated that the early use of the well-proven SYSADOA in any localization of OA, in particular the combined drugs of chondroitin sulfate and glucosamine, can increase the effectiveness of treatment, reduce possible functional disorders, and minimize the adverse effects of analgesic therapy.

The Warburg effect is characterised by increased glucose uptake and lactate secretion in cancer cells resulting from metabolic transformation in tumour tissue. The corresponding molecular pathways switch from oxidative phosphorylation to aerobic glycolysis, due to changes in glucose degradation mechanisms known as the ‘Warburg reprogramming’ of cancer cells. Key glycolytic enzymes, glucose transporters and transcription factors involved in the Warburg transformation are frequently dysregulated during carcinogenesis considered as promising diagnostic and prognostic markers as well as treatment targets. Flavonoids are molecules with pleiotropic activities. The metabolism-regulating anticancer effects of flavonoids are broadly demonstrated in preclinical studies. Flavonoids modulate key pathways involved in the Warburg phenotype including but not limited to PKM2, HK2, GLUT1 and HIF-1. The corresponding molecular mechanisms and clinical relevance of ‘anti-Warburg’ effects of flavonoids are discussed in this review article. The most prominent examples are provided for the potential application of targeted ‘anti-Warburg’ measures in cancer management. Individualised profiling and patient stratification are presented as powerful tools for implementing targeted ‘anti-Warburg’ measures in the context of predictive, preventive and personalised medicine.

Triple-negative breast cancer (TNBC) is considered one of the highest-risk subtypes of breast cancer and has dismal prognosis. Local recurrence rate after standard therapy in the early breast cancer setting can be upwards to 72% in 5 years, and in the metastatic setting, the 5-year overall survival is 12%. Due to the lack of receptor expression, there has been a paucity of targeted therapeutics available, with chemotherapy being the primary option for systemic treatment in both the neoadjuvant and metastatic setting. More recently, immunotherapy has revolutionized the landscape of cancer treatment, particularly immune checkpoint inhibitor (ICI) therapy, with FDA approval in over 20 types of cancer since 2011. Compared to other cancer types, breast cancer has been traditionally thought of as being immunologically cold; however, TNBC has demonstrated the most promise with immunotherapy use, a timely discovery due to its lack of targeted therapy options. In this review, we summarize the trials using checkpoint therapy in early and metastatic TNBC, as well as the development of biomarkers and the importance of immune related adverse events (IRAEs), in this disease process.

Background: Stratified medicine methodologies based on subgroup analyses are often insufficiently powered. More powerful personalized medicine approaches are based on continuous scores. Objective: We deployed a patient-specific continuous score predicting treatment response in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Data from two independent randomized controlled trials (RCTs) were used to build and validate an individual treatment response (ITR) score, regressing annualized relapse rates (ARRs) on a set of baseline predictors. Results: The ITR score for the combined treatment groups versus placebo detected differential clinical response in both RCTs. High responders in one RCT had a cross-validated ARR ratio of 0.29 (95% confidence interval (CI) = 0.13–0.55) versus 0.62 (95% CI = 0.47–0.83) for all other responders (heterogeneity p = 0.038) and were validated in the other RCT, with the corresponding ARR ratios of 0.31 (95% CI = 0.18–0.56) and 0.61 (95% CI = 0.47–0.79; heterogeneity p = 0.036). The strongest treatment effect modifiers were the Short Form-36 Physical Component Summary, age, Visual Function Test 2.5%, prior MS treatment and Expanded Disability Status Scale. Conclusion: Our modelling strategy detects and validates an ITR score and opens up avenues for building treatment response calculators that are also applicable in routine clinical practice.

Significance: Chronic venous disease (CVD) is prevalent in the aging population and leads to venous leg ulcers (VLUs). These wounds can last and recur for years, significantly impacting quality of life. A large body of literature exists on CVD and VLU diagnosis and treatment. Multiple algorithms, guidelines, and consensus documents have been published on this topic, highlighting the importance of this issue in clinical practice. However, these documents are not fully aligned with each other. Recent Advances: The latest update of the internationally used classification system for CVD was recently published. Our review aims to summarize the existing information to provide an educational tool for clinicians new to this topic, and to highlight the commonalities between the published recommendations. Critical issues: VLUs need to be treated with consideration for the extent of venous disease present in the patient. This requires a good understanding of the various components involved and the possible additional concomitant conditions by the first-line clinician who encounters the patient. A multidisciplinary team is necessary for a successful overall treatment plan, and this plan should be tailored to each patient's specific needs and lifestyle. Future Directions: Compression is still the mainstay of treatment for CVD and VLUs. Compression is needed long term, but it does not suffice by itself to prevent recurrences without interventional correction. Venous intervention should be offered early to prevent or slow disease progression and reduce recurrence.

Objective: Over 1 million new cases of hepatocellular carcinoma (HCC) are diagnosed worldwide every year. Its prognosis remains poor, and the 5-year survival rate in all disease stages is estimated to be between 10% and 20%. Radiofrequency ablation (RFA) has become an important local treatment for liver cancer, and machine learning (ML) can provide many shortcuts for liver cancer medical research. Therefore, we explore the role of ML in predicting the total mortality of liver cancer patients undergoing RFA. Methods: This study is a secondary analysis of public database data from 578 liver cancer patients. We used Python for ML to establish the prognosis model. Results: The results showed that the 5 most important factors were platelet count (PLT), Alpha-fetoprotein (AFP), age, tumor size, and total bilirubin, respectively. Results of the total death model for liver cancer patients in test group: among the 5 algorithm models, the highest accuracy rate was that of gbm (0.681), followed by the Logistic algorithm (0.672); among the 5 algorithms, area under the curve (AUC) values, from high to low, were Logistic (0.738), DecisionTree (0.723), gbm (0.717), GradientBoosting (0.714), and Forest (0.693); Among the 5 algorithms, gbm had the highest precision rate (0.721), followed by the Logistic algorithm (0.714). Among the 5 algorithms, DecisionTree had the highest recall rate (0.642), followed by the GradientBoosting algorithm (0.571). Conclusion: Machine learning can predict total death after RFA in liver cancer patients. Therefore, ML research has great potential for both personalized treatment and prognosis of liver cancer.

Background Contemporary treatments for functional dyspepsia have limitations. Herbal medicine has been suggested as adjunctive treatment. With growing scientific recognition and public interests, an in-depth review of this is timely. Aims/purpose To evaluate the therapeutic potential and problems that may be associated with the adoption of herbal medicines in functional dyspepsia. Methods We reviewed the treatment landscape of functional dyspepsia and assessed the scientific community's interest in herbal medicine. Preclinical pharmacological and clinical trial data were reviewed for several herbal medicines available in the market. Challenges associated with adoption of herbal medicine in mainstream medicine were critically evaluated. Results We found that herbal medicines frequently comprise a combination of herbs with multiple reported pharmacological effects on gastrointestinal motility and secretory functions, as well as cytoprotective and psychotropic properties. We identified a number of commercially available herbal products that have undergone rigorous clinical trials, involving large numbers of well-defined subjects, reporting both efficacy and safety for functional dyspepsia. Persisting concerns include lack of rigorous assessments for majority of products, toxicity, consistency of ingredients, dose standardizations, and quality control. We provide a quality framework for its evaluation. Conclusions We commend herbal medicine as a viable future option in managing functional dyspepsia. An attractive appeal of herbal medicine is the prospect to simultaneously target multiple pathophysiological mechanisms. Wider adoption and acceptance of herbal medicines in treatment algorithms of functional dyspepsia will require the application of the scientific rigor expected of chemical therapies, to all stages of their development and evaluation.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB—Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Summary In the past few years there have been major changes in the treatment landscape in oncology; lung cancer is affected by those changes like almost no other solid tumor. The rise of further second- and third-line tyrosine kinase inhibitors offers sequential therapy for patients with mutated non-small-cell lung cancer. Immunotherapy has found its way into clinical routine and presents us with new challenges in managing side effects, evaluating treatment response and deciding on how long we treat our patients. The treatment algorithm of lung cancer has changed in the last month and further practice-changing trials are coming up, so treating lung cancer patients shows nowadays a more challenging perspective with the possibility of subsequently applied individual therapies. This article provides a brief overview of the highlights presented at the ASCO (American Society of Clinical Oncology) annual meeting this year in Chicago.

Using combined endpoints to define no evident disease activity (NEDA) is becoming increasingly common when setting targets for treatment outcomes in multiple sclerosis (MS). Historically, NEDA has taken account of the occurrence of relapses, brain magnetic resonance imaging (MRI) lesions and disability worsening, but this approach places emphasis on inflammatory activity in the brain and mostly overlooks ongoing neurodegenerative damage. Combined assessments of NEDA which take account of changes in brain volume or neuropsychological outcomes such as cognitive function may begin to address this imbalance, and such assessments may also consider blood or spinal-fluid neurofilament levels or patient-reported outcomes and quality of life measures. If a combined NEDA assessment can be validated in prospective studies as indicative of long-term disease remission at the individual patient level, treating to achieve NEDA could become the goal of clinical practice and achieving NEDA may become the “new normal” state of disease control for patients with MS.

Coronary artery disease (CAD) is one of the important causes of cardiovascular morbidity and mortality globally, giving rise to more than 7 million deaths annually. An increasing burden of CAD in India is a major cause of concern with angina being the leading manifestation. Stable coronary artery disease (SCAD) is characterised by episodes of transient central chest pain (angina pectoris), often triggered by exercise, emotion or other forms of stress, generally triggered by a reversible mismatch between myocardial oxygen demand and supply resulting in myocardial ischemia or hypoxia. A stabilised, frequently asymptomatic phase following an acute coronary syndrome (ACS) is also classified as SCAD. This definition of SCAD also encompasses vasospastic and microvascular angina under the common umbrella.

Background: Treatment algorithms are considered as key to improve outcomes by enhancing the quality of care. This is the first randomized controlled study to evaluate the clinical effect of algorithm-guided treatment in inpatients with major depressive disorder. Methods: Inpatients, aged 18 to 70 years with major depressive disorder from 10 German psychiatric departments were randomized to 5 different treatment arms (from 2000 to 2005), 3 of which were standardized stepwise drug treatment algorithms (ALGO). The fourth arm proposed medications and provided less specific recommendations based on a computerized documentation and expert system (CDES), the fifth arm received treatment as usual (TAU). ALGO included 3 different second-step strategies: lithium augmentation (ALGO LA), antidepressant dose-escalation (ALGO DE), and switch to a different antidepressant (ALGO SW). Time to remission (21-item Hamilton Depression Rating Scale

OBJECTIVES: All acetabular fractures are difficult to treat surgically, but there are four types involving two columns that are particularly challenging. The choice of surgical approach is crucial. The purpose of the study was to determine and evaluate the factors influencing the choice of surgical approach for two-column acetabular fractures. We hypothesised that more accurate preoperative planning, sophisticated technical capabilities, and evolution of surgeon experience will result in more consistent use of non-extensile single surgical approaches. We also evaluated the outcomes of surgical treatment and the correlation with the surgical approach used. DESIGN: Retrospective cohort study. PATIENTS AND METHODS: A total of 156 patients with 157 acetabular fractures involving two columns (Letournel T- types and both-column) treated surgically in a 25-year period (1988-2013) were included in the study. The acetabular fractures in this study were divided into two groups according to the date of surgery: 81 in Group 1 (1998-2002) and 76 in Group 2 (2003-2013). All fractures were classified preoperatively according to the Judet and Letournel classification system and Matta's categorisation of surgical approach. Four surgical approaches were used: single Kocher- Langenbeck (KL), single ilioinguinal (II), combined Kocher- Langenbeck and ilioinguinal (KL+II), and extended iliofemoral (EIF). The efficacy of the surgical approach utilised was assessed using three parameters: anatomical reduction, surgical time and intraoperative complications. RESULTS: There was no statistical difference between Group 1 and Group 2 in the distribution of T- type (p=0.424) and both-column (p=0.425) fractures. In Group 2 more acetabular fractures were treated through single non-extensile approaches compared with Group 1 (90.8% vs. 54.3%, p

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, mainly occurring in cirrhotic livers (in 80–90% of cases) after years of chronic inflammation [1,2]. The pathogenesis of HCC is a multistep process associated with changes in the host gene expression of multiple redundant negative-growth regulatory pathways that protect cells against transformation. An imbalance between the proliferation and apoptosis of liver cells is thought to promote tumor development [3]. Annually, 3–6% of cirrhotic patients will develop HCC, mainly men with advanced liver disease. Recent trends in the USA show that men are affected three-times more frequently than women, Asians are affected twice as often as blacks and Hispanics, and blacks are affected twice as often as whites [4]. One explanation for the disproportionate effects of HCC in men may be due to the higher estrogen concentrations present in women, which suppress IL-6 production and inhibit chemically induced liver carcinogenesis [1]. Epidemiology & etiology HCC is the principal cause of death in patients with compensated cirrhosis worldwide. It is largely a problem of less developed regions, where 83% (50% in China alone) of the estimated 782,000 new cases of liver cell cancer worldwide occur (based on 2012 data) [5]. HCC is the fifth most common cancer in men (554,000 cases; 7.5% of the total) and the ninth in women (228,000 cases; 3.4% of the total) [5]. Regions of high incidence (age adjusted rates per 100,000 inhabitants per year in men) are eastern and south-eastern Asia (31.9 and 22.2, respectively). Intermediate rates occur in southern Europe (9.5) and North America (9.3), and the lowest rates are in northern Europe (4.6) and south-central Asia (3.7) [5]. The global age distribution of HCC cases is related to the dominant viral hepatitis in the underlying population and the age at which it was acquired. For example, the disease burden is highest in areas with endemic hepatitis B virus (HBV) infection, such as in sub-Saharan Africa, where the virus is mainly transmitted at birth (with >90% of these cases becoming chronic HBV carriers). However, the diagnosis of HCC often occurs later in North America and southern Europe, where the most common etiology is HBV or hepatitis C virus (HCV) acquired later in life [2]. Several factors have been reported to increase HCC risk among HBV carriers, including male sex, older age, Asian or African ethnicity, family history of HCC, viral (higher levels of HBV repli cation, HBV genotype, longer duration of infection or coinfection with HCV, HIV or hepatitis D virus), clinical (cirrhosis) and environmental or lifestyle factors (exposure to aflatoxin, chronic excessive alcohol consumption or tobacco smoking). Other risk factors that increase the risk in HCV-infected patients include coinfection with HIV, HBV, HCV genotype 1b, old age, the presence of diabetes and obesity and a high level of chronic alcohol consumption. However, both HBV and HCV are highly amenable to preventive measures with antivirals or vaccination (for HBV). In Italy, for example, the Italian Liver Cancer (ITA.LI.CA) database reveals a decline in HCV infection with a concomitant increase in alcohol consumption as the primary etiology for HCC [6].